Dynamic post-transcriptional regulation by Mrn1 links cell wall homeostasis to mitochondrial structure and function

The RNA-binding protein Mrn1 in Saccharomyces cerevisiae targets over 300 messenger RNAs, including many involved in cell wall biogenesis. The impact of Mrn1 on these target transcripts is not known, however, nor is the cellular role for this regulation. We have shown that Mrn1 represses target mRNAs through the action of its disordered, asparagine-rich amino-terminus. Its endogenous targets include the paralogous SUN domain proteins Nca3 and Uth1, which affect mitochondrial and cell wall structure and function. While loss of MRN1 has no effect on fermentative growth, we found that mrn1 Delta yeast adapt more quickly to respiratory conditions. These cells also have enlarged mitochondria in fermentative conditions, mediated in part by dysregulation of NCA3, and this may explain their faster switch to respiration. Our analyses indicated that Mrn1 acts as a hub for integrating cell wall integrity and mitochondrial biosynthesis in a carbon-source responsive manner. Author summary Regulated degradation of messenger RNAs acts together with regulated transcription to determine mRNA abundance and thereby control gene expression. RNA-binding proteins coordinate post-transcriptional gene expression programs by recognizing groups of functionally related transcripts and modulating their stability and decay. Here, we establish that the yeast RNA-binding protein Mrn1 controls a gene expression program that links the mitochondrion with the yeast cell wall. The cell wall is a dynamic structure that withstands substantial osmotic pressure while undergoing continuous remodeling during growth and division. It comprises a large fraction of the cell's dry weight and consumes substantial energy as well as carbohydrates. Mrn1 binds hundreds of target mRNAs, which are enriched for functions in cell wall organization and biogenesis. We found that Mrn1 destabilizes these targets during glucose fermentation, but its repressive effect is relieved when cells switch to respiratory growth. Cells lacking MRN1 have expanded mitochondria during glucose fermentation and adapt more quickly to respiration. The SUN domain protein Nca3 is a key Mrn1 target that is associated with both the cell wall and the mitochondrion and underlies much of these effects. Mrn1 control of Nca3 and other genes sculpts mitochondria and the cell wall in response to changing growth conditions.

Automated summary

The yeast RNA-binding protein Mrn1 is involved in controlling a gene expression program that links mitochondria with the yeast cell wall, impacting cell wall organization and biogenesis. Mrn1 destabilizes target mRNAs during glucose fermentation, but this repression is relieved when cells switch to respiratory growth, leading to expanded mitochondria and quicker adaptation to respiration in cells lacking MRN1. The SUN domain protein Nca3, a key target of Mrn1, plays a crucial role in sculpting mitochondria and the cell wall in response to changing growth conditions.